During the reporting year, the NCGC worked with over 300 researchers worldwide to advise them on assay design and development, chemistry research, informatics research, technology development projects, and to run high-throughput screens and chemically optimize small molecule leads. In collaboration with the Molecular Libraries Probe Production Centers Network (MLPCN), the U.S. Environmental Protection Agency, the National Toxicology Program, NIEHS, FDA, NCI, numerous rare disease foundations, and other intramural and extramural laboratories, the NCGC performed over 34 high-throughput screens on molecular targets and cellular phenotypes important for virtually every area of biology and disease. The NCGC also continued its work in the field of siRNA, initiating assay development on 18 projects, completing 12 pilot screens (1,000 genes), and completing 12 primary screens (7,000 22,000 genes), and moving into hit validation and follow-up on those projects. 13 new chemical probes of diverse biologies were discovered, and NCGC scientists published 56 publications during FY12. The NCGC filed 8 patent applications during this reporting period. Also during the reporting period, the NCGC deposited 243 BioAssays, 27 Summary AIDs, 13,143,171 concentration response curves, and a total of 52,572,684 data points into PubChem. NCGC continued to apply its chemistry expertise to optimizing probes; a portfolio of 19 in-house chemistry projects and 18 chemistry collaborations was maintained throughout the year. Under leadership from NCGC, along with the U.S. Environmental Protection Agency and the National Toxicology Program of NIEHS, the Toxicology in the 21st Century project (Tox21) continued to flourish. Tox21 is an initiative designed to predict the toxicity of chemicals on human health and the environment. This is accomplished by developing in vitro assays for more predictive, mechanistically-based methods than those used with current animal testing. During FY13, Tox21 continued its accelerated production phase. In the current reporting year, NCGC completed 12 full Tox21 screens and 13 smaller-scale screens and 20 follow-up experiments on specific, varied cell lines. In FY13, the Matrix Program, which takes a close look at phenotypic and combination screening for the discovery of novel drug pairs, prospered with several exciting projects. A total of 11 new projects were initiated, 5 of which have come to completion. This work could not have been feasible without the support of the NCI Major Opportunities Award, which was awarded to this program early on in FY13. The Assay Guidance manual has continued to evolve and has become a central resource for academic and industrial investigators interested in MLPCN science. In 2012, the manual was published as an eBook on the NLM/NCBI site (http://www.ncbi.nlm.nih.gov/books/NBK53196/). Since moving to the eBook format , the worldwide access statistics went from 7,099 hits in October 2012 to over 22, 094 hits in June 2013 with 10,695 unique IP addresses. This indicates , that a large number of new users are finding the Assay Guidance Manual site useful in early drug discovery and translational science applications. The manual remains a central resource for investigators interested in MLPCN science and several new chapters and revisions to the existing chapters have been added in 2013. The Book format also allows for dynamic real-time updates to the manual on a quarterly basis by expert content providers and the editorial group. Given the NCGC's continual efficiency improvement program, we were able to increase the throughput of existing robotic screening, informatics, and chemistry systems by improvements in applications, software, and utilization scheduling, driven by both the project teams and Project Management. The NCGC maintained its existing robotic technology and Bio Safety Levels 1, 2, and 3 facilities during the reporting period. The NCGC's Outreach program continued its extraordinary record of productivity during the reporting period. NCGC staff advised 219 outside investigators on assay design and assay development, and assisted over 50 investigators with chemistry, informatics, and technology development inquiries. NCGC scientists gave 72 invited presentations throughout the U.S., Europe, and Asia during the period. NCGC outreach resulted in the submission of over 74 grant applications for NIH programs. The Assay Guidance manual has continued to evolve and has become a central resource for investigators interested in MLPCN science. During the reporting period, 73,967 visits were recorded, with 144,942 page views, and 54,504 unique visitors. 56% of these visitors originated from outside the US, from a total of 157 countries. 72% of visits were new visits, indicating that a large number of new users are finding the Assay Guidance Manual site. The manual remains a central resource for investigators interested in MLPCN science. During the year, the NCGC also maintained its status as an active member of the NCI's Chemical Biology Consortium and currently has one project in progress. Finally, NCGC's work on its IATAP grants continued.